In this application, we propose to determine the feasibility of displaying a highly constrained peptide motif on the pIII coat protein of M13 filamentous phage. Upon successful display of this peptide motif, we will commence to determine whether this motif can be evolved to bind desired target molecules by randomly mutagenizing the sequences in one of the loop structures displayed by this peptide. If the studies described in this Phase I study are successful we will attempt to further evolve these molecules to recognize the targets with higher affinities by randomizing subsequent loop structures. In this manner, we hope to create a genetic platform on which to build very compact and stable binding moieties for probing biological pathways and utilization in clinical diagnostic, imaging, targeting and therapeutic protocols. PROPOSED COMMERCIAL APPLICATION: Combination libraries of small molecules that can be evolved to bind with more favorable properties will be extremely valuable tools to isolate small molecule inhibitors or activators of enzymes and receptors. These molecules will be utilized as research reagents to probe complex biological processes and clinically they can be used as diagnostic, imaging, targeting, or therapeutic agents.